Researchers have discovered a genetic mechanism involved in pain modulation in genetically engineered mice. Mice lacking a gene called DREAM (downstream regulatory element antagonistic modulator) showed a dramatic loss of pain sensitivity compared to mice that had the DREAM gene. These findings could lead scientists to an entirely new approach to pain control.
The study, conducted by the University of Toronto, The Hospital for Sick Children, and the Amgen Institute, published its results in the Jan. 11 issue of the journal Cell.
According to Professor Michael Salter, director of the University of Toronto Centre for the Study of Pain, and a senior scientist at The Hospital for Sick Children, DREAM produces a protein that suppresses the genetic machinery that reads the DNA code for dynorphin. Dynorphin is a peptide normally produced in the body, and is known as an endorphin produced in response to pain or stress. The scientists found the DREAM gene decreases dynorphin production.
“This is an exciting development,” said Salter, “There’s a great interest in this finding because it’s so different from the traditional approaches researchers have been taking to pain management.”
When the DREAM gene was absent in mice, the researchers discovered increased production of dynorphin in the region of the spinal cord involved in transmitting and controlling pain messages. They discovered the mice had decreased sensitivity to acute, inflammatory, and neuropathic pain.
“The attenuated pain response was evident for all types of pain in all types of tissue tested,” Salter said, “The fact that even mice with neuropathic pain-the kind of sharp, chronic pain resulting from nerve injury-experienced this effect is exciting because the medical community currently doesn’t have any widely effective treatments for this debilitating type of pain.”
Current approaches to pain management focus on drugs such as morphine that stimulate cell receptors for the endorphin family of proteins, also called the endogenous opioid system, or drugs such as aspirin that block the enzyme cyclo-oxygenase.
The DREAM gene, however, works in an entirely different way by binding directly to DNA and regulating the expression of a protein in the endogenous opioid system.
“These findings point to a novel pharmacological approach to pain management where researchers will be looking for drugs that could block the ability of DREAM to bind to DNA or simply prevent the production of DREAM,” Salter said.
The mice that lacked the DREAM gene were otherwise completely normal and showed no reduction in their motor function, learning, or memory. They also did not become addicted to the pain control chemicals their bodies produced, which may prove to be an advantage over the potentially addictive drugs such as morphine that act on opioid receptors.
“Pain is a huge, silent public health crisis that is only beginning to be addressed by researchers,” Salter said.